Variant 5-31409145-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001382508.1(DROSHA):c.3765T>C(p.Asn1255Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,412 control chromosomes in the GnomAD database, including 39,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4378 hom., cov: 32)

Exomes 𝑓: 0.21 ( 35297 hom. )

Consequence

DROSHA
NM_001382508.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.87

Variant links:

Genes affected

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

DROSHA links:

DROSHA (HGNC:):

DROSHA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 5-31409145-A-G is Benign according to our data. Variant chr5-31409145-A-G is described in ClinVar as [Benign]. Clinvar id is 3060031.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DROSHA	NM_001382508.1 linkuse as main transcript	c.3765T>C	p.Asn1255Asn	synonymous_variant	33/36	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5 linkuse as main transcript	c.3765T>C	p.Asn1255Asn	synonymous_variant	32/35		NP_037367.3	Q9NRR4-1
DROSHA	NM_001100412.2 linkuse as main transcript	c.3654T>C	p.Asn1218Asn	synonymous_variant	32/35		NP_001093882.1	Q9NRR4-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8 linkuse as main transcript	c.3765T>C	p.Asn1255Asn	synonymous_variant	33/36	5	NM_001382508.1	ENSP00000339845.3		Q9NRR4-1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35183

AN:

152008

Hom.:

4363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.234

GnomAD3 exomes

AF:

0.248

AC:

61656

AN:

248404

Hom.:

8586

AF XY:

0.247

AC XY:

33259

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.464

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.209

AC:

305933

AN:

1461286

Hom.:

35297

Cov.:

AF XY:

0.212

AC XY:

153783

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.264

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.311

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.232

AC:

35236

AN:

152126

Hom.:

4378

Cov.:

AF XY:

0.237

AC XY:

17601

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.255

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.463

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.199

Hom.:

4999

Bravo

AF:

0.238

Asia WGS

AF:

0.409

AC:

1419

AN:

3476

EpiCase

AF:

0.188

EpiControl

AF:

0.196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DROSHA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over